Past studies have reported that the FOXO3 is primarily regulated by multiple kinases that could phosphorylate FOXO3, which subsequently lead to nuclear exclusion and ubiquitination/degradation in the cytoplasm.35, 40 This study reports a novel regulatory mechanism of FOXO3 by BRCA1 in breast cancer where BRCA1 indirectly regulates FOXO3 expression through interfering with EZH2-H3K27me3 deposition onto the FOXO3 promoter and its DNA methylation. The gene discussed is BRCA1; the disease is breast carcinoma.